The spontaneously diabetic "BB" Wistar rat has been shown to have a syndrome akin to that of human insulin-dependent diabetics, telescoped into a short time span. Pancreatic beta cells are destroyed by an immune-related process in genetically susceptible rats, resulting in a fatal insulin-deficient, ketotic, hyperglucagonemic syndrome if untreated. This research is aimed at the elucidation of etiologic mechanisms in the beta-cell destruction with a view to ultimate prevention. A stepwise approach is being undertaken, with immune interventions using immunosuppresants at present. Concurrently, pathophysiology of insulin biosynthesis and secretion, control of glucagon secretion, and metabolic effects of the insulin deficiency is under study.